BACKGROUND: The use of radiofrequency (RF) energy has been described to perform open liver resection safely and with minimal blood loss. Yet no data are available on the potential contribution of RF energy to the limitation of intraoperative blood loss during laparoscopic liver resection (LLR). The aim of this prospective, nonrandomized study was to investigate the potential contribution of RF energy to the limitation of intraoperative blood loss in patients undergoing LLR. METHODS: Forty-five patients [male/female ratio 22/23, age 57 years (26-80)] underwent LLR. Eleven benign and 47 malignant lesions (mostly colorectal metastases) were resected. Median number [1 (1-3)] and maximum diameter [40 mm (8-170)] of tumors as well as median tumor free margins [10mm (1-30)] were comparable in patients undergoing LLR with (20 patients) or without (25 patients) RF-assistance. Thirty-eight minor (</=2 segments) and 9 major (>3 segments) resections were performed. Eighteen patients simultaneously underwent additional surgery. RESULTS: No mortality occurred. Median intraoperative blood loss was 200 (5-4000) ml and was similar in patients undergoing LLR with or without RF-assistance. The type of surgical procedure was a determinant for the amount of intraoperative blood loss (p = 0.0002). Significant bleeding occurred from large hepatic vessels at major resections. Median operation time was 115 (45-360) minutes. RF-assistance didn't seem to reduce perioperative morbidity. CONCLUSIONS: LLR can be performed with minimal intraoperative blood loss, which is determined by the type of hepatectomy. Significant intraoperative bleeding occurs from large hepatic vessels during major resections. RF-assisted parenchymal transection in LLR doesn't seem to reduce blood loss, operation time, or perioperative morbidity.